tbuckley/cabot-search huggingface dataset:
RETHINCking COPD — Bronchodilators for Symptomatic Tobacco-Exposed Persons with Preserved Lung Function?
Authors: Don D Sin
Journal: New England Journal of Medicine (2022)

Cigarette smoking is the leading global cause of chronic obstructive pulmonary disease (COPD). Worldwide, more than 1.3 billion persons smoke and 384 million persons have COPD.1 COPD is clinically diagnosed on the basis of persistent airflow limitation as measured by spirometry in persons with a history of smoking who have frequent respiratory symptoms.2 One major limitation of spirometry is that the values it measures mostly reflect pathologic processes in the large airways. However, in COPD, the disease begins in the small airways (i.e., airways <2 mm in diameter); these airways are inflamed, narrowed, and then destroyed in response to long-term . . .
Engineering Novel 3D Models to Recreate High‐Grade Osteosarcoma and its Immune and Extracellular Matrix Microenvironment
Authors: Marina Pierrevelcin, Vincent Flacher, Christopher G. Mueller, Romain Vauchelles, Eric Guerin, Benoît Lhermitte, Erwan Pencreach, Andreas Reisch, Quentin Muller, Layal Doumard, Wacym Boufenghour, Andrey S. Klymchenko, Sophie Foppolo, Charlotte Nazon, Noelle Weingertner, Sophie Martin, Claire Briandet, Véronique Laithier, Antonio Di Marco, Laurent Bund, Adeline Obrecht, Pascal Villa, Monique Dontenwill, Natacha Entz‐Werlé
Journal: Advanced Healthcare Materials (2022)

Abstract Osteosarcoma (OS) is the most common primary bone cancer, where the overall 5‐year surviving rate is below 20% in resistant forms. Accelerating cures for those poor outcome patients remains a challenge. Nevertheless, several studies of agents targeting abnormal cancerous pathways have yielded disappointing results when translated into clinic because of the lack of accurate OS preclinical modeling. So, any effort to design preclinical drug testing may consider all inter‐, intra‐, and extra‐tumoral heterogeneities throughout models mimicking extracellular and immune microenvironment. Therefore, the bioengineering of patient‐derived models reproducing the OS heterogeneity, the interaction with tumor‐associated macrophages (TAMs), and the modulation of oxygen concentrations additionally to recreation of bone scaffold is proposed here. Eight 2D preclinical models mimicking several OS clinical situations and their TAMs in hypoxic conditions are developed first and, subsequently, the paired 3D models faithfully preserving histological and biological characteristics are generated. It is possible to shape reproducibly M2‐like macrophages cultured with all OS patient‐derived cell lines in both dimensions. The final 3D models pooling all heterogeneity features are providing accurate proliferation and migration data to understand the mechanisms involved in OS and immune cells/biomatrix interactions and sustained such that engineered 3D preclinical systems will improve personalized medicine.
Pseudocatalytic Hydrogels with Intrinsic Antibacterial and Photothermal Activities for Local Treatment of Subcutaneous Abscesses and Breast Tumors
Authors: Yan Ma, Yanbin Sun, Lingling Xu, Xueqiao Li, Deyan Gong, Zhaohua Miao, Haisheng Qian
Journal: Advanced Healthcare Materials (2022)

Abstract The intimate relationship between bacteria and tumors has triggered a lot of activities in the development and design of bioactive materials to concurrently respond to antitumor and antibacterial demands. Herein, a pseudocatalytic hydrogel (AM‐I@Agar) with intrinsic antibacterial and photothermal activities, synthesized by incorporating prefabricated amylose‐iodine nanoparticles into low‐melting‐point agarose hydrogel, is explored as a bioactive agent for local treatment of subcutaneous abscesses and breast tumors. The AM‐I@Agar hydrogel depicts the ability of pseudocatalytic O 2 generation from H 2 O 2 to alleviate hypoxia. Meanwhile, the AM‐I@Agar hydrogel exhibits temperature self‐regulation features, beneficial for avoiding thermal injury during photothermal therapy owing to thermochromic properties. Upon local injection into a subcutaneous abscess, methicillin‐resistant Staphylococcus aureus is effectively eliminated by the AM‐I@Agar hydrogel, and complete skin recovery is achieved in 8 d, demonstrating much better antibacterial effects compared with penicillin, a small‐molecule antibiotic. AM‐I/5‐FU@Agar hydrogel, obtained after loading 5‐fluorouracil (5‐FU), significantly inhibits tumors in both normal 4T1 tumor‐bearing mice and MRSA‐infected 4T1 tumor‐bearing mice models via a synergistic photothermal‐chemo effect, and shows treatment efficiency superior to that achieved with photothermal therapy or 5‐FU alone. This work provides a concept for the design and development of bioactive agents for potential management of bacteria‐associated cancer.
The Care of the Patient
Authors: Pauline L. Rabin
Journal: JAMA (1984)

This classic essay, with its fabric of pristine humanism, its universality, and its timelessness, embodies the noblest aspirations of the medical profession. Peabody gave his address at the Harvard Medical School during a course on the care of the patient. Dr Joseph Pratt<sup>1</sup>was in the audience and subsequently wrote: "After the lecture I talked with Dr. Peabody. His address doubtless made a deep impression on the audience but there was no evidence of unusual approval. In a few minutes the hall was emptied and we were alone." Since that day in 1926, Peabody's words have become a paradigm for all physicians. <h3>On the Patient as Person</h3> His essay covers three chief topics. The first is the importance of individualizing medical care. Long before the introduction of the SMAC 46 battery, to which so many patients are subjected even before they see their physician, Peabody cautioned the medical profession
Traumatic Rupture of Aorta
Authors: Robert M. Greendyke
Journal: JAMA (1966)

Forty-two cases of traumatic rupture of the aorta were encountered in 1,259 medicolegal autopsies performed in a four-year period. One of every six victims of fatal auto accidents sustained aortic rupture. This lesion was generally associated with accidents characterized by violent and sudden deceleration. Thirteen of 25 passengers and drivers sustaining aortic rupture were ejected from the automobiles. It is important to consider the possibility of aortic rupture in survivors of automobile crashes.
Air Force Football Injuries
Authors: Maurey L. Allen
Journal: JAMA (1968)

A clinical and statistical study of football injuries at an overseas air force base recorded 290 injuries. Of these, 111 were major football injuries. The knee was the most frequently injured area, and sprains were the most frequent type of disabling injury. Thirty-eight players were hospitalized, 22 players were operated upon, and 65 players received injuries such that they were unable to finish out the season. There were no deaths. The number of players competing was 465. There were 34 games among five teams during the 20-game 1965 season and the first 14 games of the 1966 season. The classification of these injuries and their grading by degree of severity is accomplished through the use of the<i>AMA's Standard Nomenclature of Athletic Injuries</i>.
The Contract for Health Care
Authors: Donnell D. Etzwiler
Journal: JAMA (1973)

Health care in the United States is undergoing a significant transition. Numerous concerns and criticisms have been expressed regarding the quality, quantity, and cost of medical care. In the April 24, 1972, issue of<i>JAMA</i>, we discussed the present status of patient education and pointed out the need for patients (consumers) to assume an active role in the management of chronic diseases or maintenance of normal health. Consumer participation, however, can be effective only if patients are properly prepared to assume their responsibilities and are accepted as members of the health care team. Currently, patient education and participation is not regarded as an integral part of quality medical care. In a recent national survey we conducted among physicians, nurses, and dietitians, the greatest difficulty in the treatment of a chronic disease was reported to be "a lack of patient knowledge and understanding about his disease and its management." Even federal
Prevention of Catheter-Associated Urinary Tract Infection
Authors: Dennis G. Maki
Journal: JAMA (1972)

Catheter-associated urinary tract infection (UTIc) is a significant infection hazard despite available methods of prevention. Many UTIc pathogens are transmitted between catheterized patients by passive carriage on the hands of attendants. A recent study of Serratia marcescens UTIc demonstrated that the risk of urinary tract colonization varied directly with the extent of clustering of such patients. Their geographic dispersal, especially separation of those infected from those noninfected, warrants trial as an adjunctive measure for prevention of UTIc.
Diabetes and the Risk of Stroke
Authors: Robert D. Abbott
Journal: JAMA (1987)

From 1965 to 1968, the Honolulu Heart Program began following up a cohort of men in a prospective study of cardiovascular disease. For this report, we examined the 12-year risk of stroke in 690 diabetic and 6908 nondiabetic subjects free of coronary heart disease and a history of stroke at study entry. In 12 years of follow-up, 62.3 per 1000 diabetic men and 32.7 per 1000 nondiabetic men experienced a stroke. The relative risk of thromboembolic stroke for those with diabetes compared with those without diabetes was 2.0 (95% confidence limits, 1.4 to 3.0). Although diabetes was usually associated with an atherogenic risk profile, control of hypertension, complicating myocardial infarction, and other risk factors failed to diminish the effect of diabetes on stroke. Among those without diabetes, the relative risk of thromboembolic stroke for those at the 80th percentile of serum glucose level compared with those at the 20th percentile (199 vs 115 mg/dL [11.0 vs 6.4 mmol/L]) was 1.4 (95% confidence limits, 1.1 to 1.8). In the nondiabetic sample, the relative risk of thromboembolic stroke for those with glucosuria compared with those without glucosuria was 2.7 (95% confidence limits, 1.6 to 4.5). There was no association between diabetes, or measures of glucose intolerance, and hemorrhagic stroke. We conclude that diabetes, even in a possibly undiagnosed subset of hyperglycemic individuals, imparts an additional independent risk of stroke unexplained by clinically measured risk factors. (<i>JAMA</i>1987;257:949-952)
Sociodemographic Characteristics of Cigarette Smoking Initiation in the United States
Authors: Luis G. Escobedo
Journal: JAMA (1990)

Cigarette smoking initiation greatly influences smoking prevalence in the United States. To understand better the initiation of cigarette smoking, we estimated the age-specific incidence of cigarette smoking initiation in relation to race/ethnicity, sex, and educational attainment, using the reported age at smoking onset for 18- to 35-year-old respondents in the 1987 National Health Interview Survey (N = 14 764) and the Hispanic Health and Nutrition Examination Survey (N = 3123) conducted during 1982 to 1984. Among white, black, and Hispanic respondents the incidence of smoking initiation increased rapidly after 11 years of age, reaching a peak in groups 17 to 19 years of age, rapidly declining in groups through age 25 years, and gradually declining thereafter. Age-specific smoking initiation rates were generally lower among black than white respondents, similar between white and Hispanic respondents, and appreciably higher among black and Hispanic men than women. Compared with persons who graduated from high school, persons with less than high school education were consistently more likely to start smoking cigarettes during childhood and adolescence. These data indicate that age and educational attainment are the factors most consistently associated with cigarette smoking initiation among all race/ethnic groups in the United States. These data also emphasize the need for smoking-prevention education beginning at an early age, particularly among persons of low socioeconomic status. (<i>JAMA</i>. 1990;264:1550-1555)
Serological Response to Syphilis Treatment
Authors: Stuart T. Brown
Journal: JAMA (1985)

One important aspect of the posttreatment evaluation of patients with early syphilis is assessment of serological test results. Using information previously collected from 818 patients in the Early Syphilis Study, we evaluated the seroresponse of people treated for primary or secondary syphilis. We generated curves describing the VDRL titer declines with time. The VDRL titer declined approximately fourfold at three months and eightfold at six months. These observations will allow clinicians to identify treatment failures or reinfections at the earliest possible time during their follow-up. (<i>JAMA</i>1985;253:1296-1299)
Organizing an Academic Nursing Home
Authors: Darryl Wieland
Journal: JAMA (1986)

In March 1984, a program for an academic nursing home was established at the Sepulveda Veterans Administration Medical Center. The program was designed to improve care of nursing home patients, provide interdisciplinary training for medical house staff and allied health students, and stimulate research. Geriatric faculty physicians were appointed, medical house staff were assigned as primary physicians to groups of patients, and geriatric nurse practitioners were hired to provide day-to-day care. A two-phase evaluation of the impact of the academic nursing home on patient care was conducted. Beneficial developments associated with the program in concurrent comparison with the standard nursing home unit included a significant decrease in patient transfers to the acute-care hospital and significant improvements in functional status, patient satisfaction, and morale. A trend toward improved survival was nonsignificant. Longer-term follow-up revealed a significantly increased rate of discharge for patients completing long-term rehabilitation. Overall, the costs of nursing home care were only minimally increased by the program. Results suggest that programs like the academic nursing home can lead to improved process and outcomes of nursing home care. (<i>JAMA</i>1986;255:2622-2627)
Fibrinogen and Risk of Cardiovascular Disease
Authors: William B. Kannel
Journal: JAMA (1987)

During the tenth biennial examination of the Framingham Study, 1315 participants who were free of cardiovascular disease had fibrinogen levels measured. During the ensuing 12 years, cardiovascular disease developed in 165 men and 147 women. For both sexes, the risk of cardiovascular disease was correlated positively to antecedent fibrinogen values higher than the 1.3 to 7.0 g/L (126 to 696 mg/dL) range. The magnitude of the risk diminished with advancing age in women but not in men. Risk for coronary heart disease also was significantly related to fibrinogen level. Here, the magnitude of risk displayed diminishing impact with age, again only in women. Risk of stroke increased progressively with fibrinogen level in men but not in women. The impact of fibrinogen value, considered as a separate variable, on cardiovascular disease was comparable with the major risk factors, such as blood pressure, hematocrit, adiposity, cigarette smoking, and diabetes. Fibrinogen values were also significantly related to these risk factors. Taking all these into account in a multivariate analysis, fibrinogen level was still significantly related to the incidence of cardiovascular disease in men and marginally significant in women. For coronary heart disease, the fibrinogen level was significant for both men and women. Elevated fibrinogen level is a predictor of cardiovascular disease that should be added to the cardiovascular risk factor profile. (<i>JAMA</i>1987;258:1183-1186)
Mortality in relation to smoking: 20 years' observations on male British doctors.
Authors: R Doll, R Peto
Journal: BMJ (1976)

In 1951 the British Medical Association forwarded to all British doctors a questionnaire about their smoking habits, and 34440 men replied. With few exceptions, all men who replied in 1951 have been followed for 20 years. The certified causes of all 10 072 deaths and subsequent changes in smoking habits were recorded. The ratio of the death rate among cigarette smokers to that among lifelong non-smokers of comparable age was, for men under 70 years, about 2:1, while for men over 70 years it was about 1-5:1. These ratios suggest that between a half and a third of all cigarette smokers will die because of their smoking, if the excess death rates are actually caused by smoking. To investigate whether this is the case, the relation of many different causes of death to age and tobacco consumption were examined, as were the effects of giving up smoking. Smoking caused death chiefly by heart disease among middle-aged men (and, with a less extreme relative risk, among old men,) lung cancer, chronic obstructive lung disease, and various vascular diseases. The distinctive features of this study were the completeness of follow-up, the accuracy of death certification, and the fact that the study population as a whole reduced its cigarette consumption substantially during the period of observation. As a result lung cancer grew relatively less common as the study progressed, but other cancers did not, thus illustrating in an unusual way the causal nature of the association between smoking and lung cancer.
The Effects of Limitation of Activity Upon the Human Body
Authors: Frederic J. Kottke
Journal: JAMA (1966)

The functional capacity of any organ is dependent within physiological limits upon the intensity and frequency of its activity. Although rest may be protective for a damaged organ it results in progressive loss of functional capacity for normal organs. Limitation of activity during prolonged bed rest causes significant deterioration of multiple organ systems including the skeletal, neuromuscular, cardiovascular, respiratory, urogenital, and nervous systems. Total inactivity of muscle results in loss of strength of approximately 3% per day. Neuromuscular and emotional control and intellectual performance are all impaired by prolonged bed rest. Cardiovascular function decreases during bed rest more rapidly than it is restored when activity is resumed. Years may be required to restore the calcium lost from the skeleton during immobilization.
Mechanisms of Contraction of the Normal and Failing Heart
Authors: Eugene Braunwald, John Ross, Edmund H. Sonnenblick
Journal: New England Journal of Medicine (1967)

THE function of the heart is to propel unoxygenated blood to the lungs and to deliver oxygenated blood to the peripheral tissues in accordance with their metabolic requirements. Since William Harvey's discovery of the pumping action of the heart, physiologists have asked two fundamental questions concerning the contraction of the heart: what are the events that constitute a normal cardiac contraction, and how are these events controlled so that the normal heart can adjust its performance almost instantly to meet the rapidly varying requirements of the peripheral tissues? The clinician has added a third question: how are these events disturbed . . .
Unexplored therapeutic opportunities in the human genome
Authors: Tudor I. Oprea, Cristian G. Bologa, Søren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schürer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dušica Vidović, Anna Waller, David Westergaard, Jeremy J. Yang, Gergely Zahoránszky-Köhalmi
Journal: Nature Reviews Drug Discovery (2018)
Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses
Authors: Shilin Chen, Zheng Li, Sanyin Zhang, Yuxin Zhou, Xiaohe Xiao, Pengdi Cui, Binjie Xu, Qinghe Zhao, Shasha Kong, Yuntao Dai
Journal: Acta Pharmaceutica Sinica B (2022)

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.
High response rates with single-agent belantamab mafodotin in relapsed systemic AL amyloidosis
Authors: Jahanzaib Khwaja, Joshua Bomsztyk, Shameem Mahmood, Brendan Wisniowski, Raakhee Shah, Anish Tailor, Kwee Yong, Rakesh Popat, Neil Rabin, Charalampia Kyriakou, Jonathan Sive, Simona Degli Esposti, Daniel F. P. Larkin, Sarah Worthington, Alyse Hart, Emma Dowling, Nuno Correia, Ceri Bygrave, Andrzej Rydzewski, Krzysztof Jamroziak, Ashutosh D. Wechalekar
Journal: Blood Cancer Journal (2022)
Structural repurposing of SGLT2 inhibitor empagliflozin for strengthening anti-heart failure activity with lower glycosuria
Authors: Yixiang Xu, Chao Zhang, Kai Jiang, Xinchun Yang, Feng Chen, Zhiyang Cheng, Jinlong Zhao, Jiaxing Cheng, Xiaokang Li, Xin Chen, Luoyifan Zhou, Hao Duan, Yunyuan Huang, Yaozu Xiang, Jian Li
Journal: Acta Pharmaceutica Sinica B (2022)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.